The persistence and resistance of the prion agents responsible for CJD (Creutzfeldt-Jakob disease) has raised fears about the possibility of iatrogenic transmission following surgery. The prion diseases, which include scrapie, atypical scrapie in sheep, BSE (Bovine Spongiform Encephalopathy) in cattle, CWD (Chronic Wasting Disease) in deer and CJD in humans are a novel group of transmissible, fatal neurodegenerative conditions. The transmissible agent termed a prion is comprised largely or solely of a conformational isomer of a normal cellular PrPC prion protein. The disease related conformer, designated PrPSc, has several unusual properties including resistance to proteolysis, detergent insolubility and high thermal stability. These physical properties coupled to observations that PrPSc adheres strongly to surgical steel and other materials present problems in the cleaning and sterilisation of surgical instruments as prion infectivity is known to be resistant to conventional autoclaving.
In the absence of a pre-clinical diagnostic test for CJD, pre-surgical testing of patients is not possible. Although in a minority of cases where CJD is suspected or confirmed, used instruments can be quarantined or destroyed. However, for the majority of procedures, new methods of decontamination are required. There are many ongoing efforts, including those by the UK Department of Health (e.g. Medical Research Council (MRC) Prion Unit, London, UK), attempting to address the problem of iatrogenic CJD transmissions.
Standard autoclaving, and in some cases high temperature autoclaving to 134° C., is the hospital standard for prion decontamination. However, conventional studies have shown survival of prions under autoclave conditions (Taylor, D M., J. Hosp. Infect. 43:S69-S76 (1999); Jackson et al., J. Gen. Virol 86:869-878 (2005)). Clearly prions will gradually accumulate under these conditions. Even the most effective autoclave will only sterilize to the degree that heat and steam penetrate the articles being treated. This is not straightforward when dealing with surgical sets comprising numerous complex instruments.
Taylor (Taylor D. M., supra) discloses the use of sodium hypochlorite solutions and 2M sodium hydroxide in prion inactivation. However, there are problems with this approach such as incomplete inactivation and incompatibility with many medical devices. Furthermore, resistance of prions to autoclaving is reported.
The WHO (World Health Organization) guidelines on prion decontamination recommend autoclaving and immersing contaminated instruments in 1M NaOH and/or 20,000 ppm NaOCl (WHO report “Infection Control Guidelines for Transmissible Spongiform Encephalopathies”, Mar. 23-26 1999, Geneva, Switzerland, WHO/CDS/CSR/APH/2000.3). This is an extremely hazardous procedure and can leave undesirable salt residues on surfaces. Furthermore, in addition to the safety aspects, the corrosive effect of such alkali or oxidizing halogen species at that concentration, combined with the temperatures and pressures implicit to autoclaving, would be likely to destroy or at least seriously damage delicate surgical instruments.
Commercial reagents currently in use for cleaning of surgical instruments prior to autoclaving have little or no effect upon PrPSc contamination. Existing methods of decontamination such as those involving LpH® and LpH®se (Steris, Inc. Mentor, Ohio), and Endozyme Plus (Ruhof Corp., Mineola, N.Y.) are of limited use in destroying infectivity. Furthermore, some reagents are incompatible with medical materials such as Dracom polymer (polysulfone).
Fichet et al. (Lancet 364:521-526 (2004)) describe three methods for disinfection of prion contaminated medical devices. Firstly they describe use of an enzymatic cleaner (KLENZYME®, Merck & Co., Inc., Whitehouse Station, N.J.) with autoclaving at 121° C. Secondly they describe alkaline cleaner (HAMO™ 100 PID, Steris, Mentor, Ohio). The third method described is the only one said to be suitable for fragile devices such as endoscopes and involves use of the alkaline cleaner on wet instruments followed by a dry vaporized hydrogen peroxide (VHP) treatment. Fichet et al. also disclose enzymatic cleaner followed by VHP treatment as being very effective. There is no disclosure of the composition of the enzymatic cleaner. Peracetic acid is used and shown to be ineffective (100% onward transmission rate following treatment).
The present invention seeks to overcome problem(s) associated with the prior art by providing effective prion decontamination compositions and methods.